# GAMMA INTERFERON--REGULATORY AND ANTITUMOR EFFECTS

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 1993 · $213,459

## Abstract

Gamma interferon (IFN-gamma) is an important lymphokine and biological
response modifier in host defense against cancer and various infectious
diseases.  It is well known as an enhancer or activator of macrophage,
natural killer cell, and T-cell cytotoxicity against tumors.  More
recently, it has been shown that secretion of IFN-gamma is an essential
part of the mechanism of action of tumor infiltrating lymphocytes.  The
objective of this proposal is to determine the structural basis for gamma
interferon (IFN-gamma) activation of cells at the receptor level, which
will ultimately facilitate the rational design of drugs with IFN-gamma
agonist/antagonist properties.  The approach is three-fold, involving
IFN-gamma and receptor synthetic peptides, recombinant IFN-gamma mutants,
and modeling based primarily on determination of the solution structure
of IFN-gamma peptides and recombinant molecules using multidimensional
nuclear magnetic resonance.  The objectives will be achieved through the
following specific aims: 1. Further characterization of the structural
basis for the binding of N-terminal and C-terminal regions of IFN-gamma
to receptor using residue substitutions, peptide truncations, and
N-terminal and C-terminal peptides complexed together. 2. Identify sites
on the IFN-gamma receptor that interact with receptor-binding domains of
IFN-gamma. 3. Develop agonists/antagonists of IFN-gamma with high
specific activity through peptide engineering and recombinant DNA
technology. 4. Determine the solution structure of IFN-gamma-receptor
binding domains as well as binding domains on receptor using
state-of-the-art multidimensional nuclear magnetic resonance (NMR). 5.
Determine the precise structural basis for binding of IFN-gamma to
receptor by determining the solution structure of IFN-gamma
receptor-binding domain alone and complexed to soluble receptor. 6. Use
agonists/antagonists of IFN-gamma activity both in vivo and in tissue
culture to assess their effects on IFN-gamma mediated functions.
Finally, mutation and peptide and protein engineering that would increase
IFN-gamma binding and agonist activity could lead to the creation of
"superferons".

## Key facts

- **NIH application ID:** 3176667
- **Project number:** 2R01CA038587-09
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **SAM.gov UEI:** NNFQH1JAPEP3
- **Principal Investigator:** HOWARD M JOHNSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $213,459
- **Award type:** 2
- **Project period:** 1984-12-01 → 1998-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3176667

## Citation

> US National Institutes of Health, RePORTER application 3176667, GAMMA INTERFERON--REGULATORY AND ANTITUMOR EFFECTS (2R01CA038587-09). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3176667. Licensed CC0.

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